The repair, as well as the replacement, of diseased and damaged human bone have been the subject of substantial research efforts over the past several decades. This research has yielded advances in the reconstruction of many areas of the human skeletal system. As a result of these advances, bone replacements and repair are presently being undertaken in several areas including the restructuring of the craniofacial system, bone repair, the introduction of artificial knee and hip joints, and the application of additional features during cosmetic surgery.
The biological mechanisms underlying the reconstruction and repair varies according to the type of bone implant selected. New bone can be formed by three basic mechanisms: osteogenesis, osteoconduction and osteoinduction. In osteogenic transplantation, viable osteoblasts and osteoclasts are moved from one body location to another where they establish centers of bone formation. Allologous tissue, cancellous bone and marrow grafts provide such viable cells. As a generalization, spongy cancellous bone permits rapid and usually complete revascularization.
In the transplantation of large segments of cortical bone or allogenic banked bone, direct osteogenesis does not occur. In these cases, osteoconduction transpires—the dead bone acts as a scaffold for the ingrowth of blood vessels, followed by the resorption of the implant and deposition of new bone. This process is slow, sometimes requiring years to reunite a large segmental defect. As a generalization, cortical bone has high strength and undergoes osteoclastic digestion of the bone and revascularizes through pre-existing anatomical channels, a relatively slow process.
Osteoinduction is the phenotypic conversion of connective tissue into bone by an appropriate stimulus. As this concept implies, formation of bone can be induced at even non-skeletal sites. Osteoinduction is the preferred method of providing new bone growth as allografts of this type are typically incorporated into the host bone within several weeks. In contrast, osteoconductive grafts have been found to be non-incorporated as long as one year after implantation.
In order to provide an environment suitable for osteoinduction, a material should be selected which is not only capable of inducing osteogenesis throughout its volume, but is also biocompatible, non-inflammatory, and possesses the ability to be ultimately resorbed by the body and replaced with new, natural bone.
During surgery, the allograft implants are manipulated to fit a given site and may be required to be folded or wrapped around a boney defect to provide the osteoconductive material thereto.
There thus exists a need for a flexible bone sheet with high tear strength which is easy to use and promotes rapid bone growth.
Initial attempts to manufacture and obtain bone sheets are shown in U.S. Pat. No. 2,621,145 in which particles of bone 1–2 mm in size were placed on a sterile carrier strip of material. The bone particles were sprayed or dripped with a citrated or heparinized plasma on the flexible carrier strip, made of a plastic material such as cellophane, to form a bone mat.
One approach to sheet type bone repair and reconstruction is disclosed in U.S. Pat. Nos. 4,472,840 and 4,394,370, the later being a divisional of the '840 patent. These patents are directed toward bone graft material, using a complex of reconstituted collagen and demineralized bone particles. This material may be fabricated into a number of forms, such as a thin membrane. One advantage of this material, as stated in the reference, is in its ability to promote bone regeneration and the use of bone particles in implant materials has been shown to induce greater quantities of new bone growth than unmodified, larger particles such as blocks or chips. Moreover, large, unmodified sections of demineralized bone are noted in the reference to induce osteogenesis only at their surface, not within the graft itself.
U.S. Pat. Nos. 4,485,096 and 4,485,097 disclose the use of bone particulates, or powders incorporated into hydrated collagen lattices contracted with fibroblast cells. The material may, if desired, be cast into sheets. One method requires the material to be coated onto a mesh of polytetrafluoroethylene (PTFE) or stainless steel which serves to maintain the length and width of the material. The inclusion of such a dimensional stabilizing material is required due to the presence of fibroblast cells because if left unrestrained, the collagen lattice would undergo contractions in all dimensions.
A related type of bone material is found in U.S. Pat. No. 4,430,760 which discloses a bone prosthesis comprising demineralized bone or dentin powder contained in a porous, medical grade casing manufactured from biocompatible polymeric fibers or a micro porous membrane. Demineralized bone powder is used as a particulate as it is more readily invaded by osteogenic cells than solid, one-piece demineralized bone. Another bone sheet is disclosed in U.S. Pat. No. 5,507,813 which utilizes elongate demineralized bone particles obtained by milling or shredding bone. The sheet is formed by a wet layering process in which slurry is applied to a porous support and the same is drained and dried to form a composite sheet with a median thickness of from about 0.002 mm to about 1.0 mm.
Yet another material is described in U.S. Pat. No. 4,678,470 which provides a bone grafting material which is produced from allogenic or xenogenic bone which may be pulverized, used as a large block, or machined into a precise predetermined shape depending on the bone defect being repaired. The method for deriving the material comprises tanning the bone with glutaraldehyde. This treatment of the material by tanning is noted as stabilizing the material as well as cross-linking the proteins. The bone may also be demineralized. The resulting demineralized bone is noted to have a “spongier” texture and thus finds use only in non-weight bearing situations, i.e., repair of small defects, filling of small tunnels or other hollow areas, cosmetic surgery, and similar uses.
A shaped bone piece which is cut to the desired usage shape is described in U.S. Pat. No. 5,053,049. The shaped piece is demineralized and tanned with a tanning reagent.
A bone sheet which is cut from organic bone matrix is disclosed in U.S. Pat. No. 5,306,304. In this reference, natural bone after having been cleaned of blood and lipid residue, is cut with a diamond wafering blade into a sheet having a thickness ranging from 0.05 to about 1.5 millimeters. The bone sheet is then demineralized until the sheet is flexible (bent or deformed from original configuration) for primary use in dental related implants.
U.S. Pat. Nos. 5,464,439 and 5,556,430 to the same inventor as the '304 patent are also directed toward the cutting of a thin sheet of bone from natural bone, the sheet having a thickness ranging from about 0.05 mm to about 1.5 mm and then demineralizing the same.
Another U.S. Pat. No. 5,899,939 is directed toward the construction of a multiple layer sheet of bone with fully mineralized or partially demineralized cortical bone. In addition to cortical bone, other materials such as hydroxyapatite can be used for the layer composition. The cortical portion of bone is taken from the diaphyseal region and cut into various thickness using a diamond bladed saw. The cortical bone layers of varying width are monolithic sections or multi-component sections and the layers, both bone and other materials, are adhesively secured together.
U.S. Pat. No. 4,950,296 shows the use of a cortical dowel having a cavity into which a cancerous plug is inserted to aid in bone formation.
Other processes used in the field of periodontics also utilize an expanded polytetrafluoroethylene material, e.g., GORETEX® e-PTFE, which is stated to be flexible and biocompatible.
Thus, and despite the processes and materials known in the art, there exists a need for a bone sheet material that possesses all of the aforementioned advantageous properties, e.g., biocompatible, non-inflammatory, capable of inducing osteogenesis, the ability to be ultimately resorbed by the body and replaced with natural bone, while not sacrificing flexibility, strength or dimensional stability thereof.